Integrated ingestible event marker system with pharmaceutical product

ABSTRACT

A system and method are provided for securing an ingestible electronic device to a pharmaceutical product without damaging the ingestible electronic device. The product includes the ingestible electronic device being placed on the product in accordance with one aspect of the present invention, in accordance with another aspect of the present invention, the ingestible electronic device is placed inside the product. Various embodiments are disclosed in accordance with the present invention for protecting and/or coating of the electronic marker as well as securing the ingestible electronic device onto the product.

CROSS-REFERENCE AND RELATED APPLICATION

Pursuant to 35 U.S.C. §119 (e), this application claims priority to thefiling date of U.S. Provisional Patent Application Ser. No. 61/266,103filed on Dec. 2, 2009 and titled INTEGRATED INGESTIBLE EVENT MARKER.SYSTEM WITH PHARMACEUTICAL PRODUCT, the disclosure of which applicationis incorporated herein by reference.

This application is related to and incorporates by reference thefollowing applications: U.S. Provisional Application Ser. No. 61/416,150field on Nov. 22, 2010 and titled INGESTIBLE DEVICE WITH PHARMACEUTICALPRODUCT; U.S. application Ser. No. 12/447,172 filed on Oct. 25, 2007 andtitled CONTROLLED ACTIVATION INGESTIBLE IDENTIFIER; U.S. ProvisionalApplication 60/862,925 filed on Oct. 25, 2006 and titled CONTROLLEDACTIVATION PHARMA-INFORMATICS SYSTEM; PCT Application US2007/82563 andfiled on Oct. 25, 2007 and titled CONTROLLED ACTIVATION INGESTIBLEIDENTIFIER.

FIELD OF INVENTION

The present invention relates to electronic devices with partial powersources and, more specifically, to electronic devices secured to apharmaceutical product wherein the electronic devices are activated uponcontact with a conducting fluid.

BACKGROUND

Pharmaceutical products are delivered to a user in many form, includinga pill Integration of a pharmaceutical product with an ingestible deviceis often a challenge due to the delicate nature of the electroniccomponents as well as the difficulty in securing the electroniccomponents to the pharmaceutical product, such as a pill or tablet orcapsule. For example, tablets are typically made using a press thatapplies pressure to a powder form. The pressures produced by the presscan often damage the electronic components that are placed inside thetablet or pill. Additionally, securing the electronic component to thesurface of tablet using adhesive material often results in damage to thedevice caused by the adhesive, which may be a thermally or chemicallyactivated type of adhesive. Furthermore, handling a small electronicdevice is often a challenge during the assembly process. Therefore, whatis needed is a system and method for securing an ingestible electronicdevice to a pharmaceutical product without damaging the ingestibleelectronic device.

SUMMARY

The present invention provides a system and method for securing aningestible electronic device to a pharmaceutical product withoutdamaging the ingestible electronic device. The product includes anelectronic marker placed on the product in accordance with one aspect ofthe present invention. In accordance with another aspect of the presentinvention, the electronic marker is placed inside the product Variousembodiments are disclosed in accordance with the present invention thatallow for protection and coating of the electronic marker.

DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention,

FIG. 1A shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention,

FIG. 1B shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention.

FIG. 1C shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention,

FIG. 2 is an exploded view of the device assembly of FIG. 1.

FIG. 2A is an exploded view of the device assembly of FIG. 1A.

FIG. 2B is an exploded view of the device assembly of FIG. 1B.

FIG. 2C is an exploded view of the device assembly of FIG. 1B.

FIG. 3A shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention.

FIG. 3B shows a first tablet portion with a device assembly secured onone surface and a second tablet portion secured over the device assemblyin accordance with one aspect of the present invention.

FIG. 3C shows a device assembly with a laminated coating in accordancewith one aspect of the present invention.

FIG. 4 shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention.

FIG. 5 shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention.

FIG. 5A shows the assembling process of the tablet of FIG. 5.

FIG. 5B shows the assembling process of the tablet of FIG. 5.

FIG. 6 shows a tablet with a device assembly secured on one surface inaccordance with one aspect of the present invention.

FIG. 6A shows the assembling process of the tablet of FIG. 6.

FIG. 7 shows a tablet with a device assembly secured on one surface anda coating that surrounds the tablet in accordance with one aspect of thepresent invention.

FIG. 8 shows a capsule with a device assembly secured on one end inaccordance with one aspect of the present invention.

FIG. 9 shows a capsule with a device assembly secured on the sidesurface in accordance with one aspect of the present invention.

FIG. 10 is a flow process for assembling a device on a tablet inaccordance with one aspect of the present invention.

FIG. 11 is a flow process for assembling a device on a tablet inaccordance with one aspect of the present invention.

FIG. 12 is a flow process for assembling a device on a tablet inaccordance with one aspect of the present invention.

FIG. 13 is a flow process for assembling a device in a tablet inaccordance with one aspect of the present invention.

FIG. 14 is an assembling apparatus for assembling a device on a tablet.

FIG. 15 is a close-up view of a portion of a portion of the apparatus ofFIG. 14 with specific indication of the direction of force applied.

FIG. 16 is a close-up view of a portion of a feeder assembly of theapparatus of FIG. 14.

FIG. 17 is a close-up view of a portion of a feeder assembly that can beused with the apparatus of FIG. 14 in accordance with another aspect ofthe present invention.

FIG. 18A is a close-up view of a portion of a feeder assembly that canbe used with the apparatus of FIG. 14 in accordance with another aspectof the present invention.

FIG. 18B is a close-up view of a portion of the feeder assembly shown inFIG. 18A at an advanced stage in the loading process.

FIG. 19 is an assembly apparatus for the assembly of a device on atablet in accordance with one aspect of the present invention.

FIG. 20 is a close-up view of a portion of the assembly apparatus ofFIG. 19.

FIG. 21 is a view of the assembly apparatus that includes additionalcomponents used in assembling the device onto a tablet or pill as shownpartially in FIG. 19.

FIG. 22 is a close-up view of a pressing tool in accordance with oneaspect of the present invention.

FIGS. 23A-C show an assembly apparatus for assembling a device onto atablet according to another aspect of the present invention.

FIGS. 24A-C show a process for loading a feeder or a feeder assembly ofany of FIG. 16, FIG. 17, FIG. 18A, and FIG. 185.

FIG. 25 shows an assembly apparatus using a process for assembling adevice onto a tablet or pill in accordance with another aspect of thepresent invention.

DETAILED DESCRIPTION

The present invention discloses multiple approaches to securing a devicecapable of indicating the occurrence of an event, such as ingestion, toan ingestible product, such as a pharmaceutical product in the form of apill or tablet. In order to better understand the process and systemsinvolved the systems are described in greater detail with respect to thedevices being secured within the product as well as the devices beingsecured onto the product's outer surface. For example, the process ofsecuring the device onto the product may be done using pressure,temperature, chemical reactions or a combination thereof. In accordancewith one aspect of the present invention, the device is protected fromthese conditions through the various securing layers and protectivelayers disclosed herein. The materials used are effective in temperatureranges are 25-200 degrees Celsius, including a target range of 80-150degrees Celsius and the duration of exposure time to such temperatures.The exposure times will vary from 0.1 sec to 50 sec, including a targetrange of 1 sec to 15 sec. Additionally, the device will be protectedfrom forces involved, which range from 1 to 50 pounds, including 2-8pounds, as well the pressures exerted during integration of the devicewith the pill, which pressures range from 100-400 PSI. Thus, the scopeof the present invention includes use of materials to protect the deviceand product from the various environmental parameters (such as pressure,time, forces, chemical reactions, and combinations thereof) associatedwith the integration of the device with the pill.

Furthermore, the scope of the present invention is not limited by theshape or type of product. For example, the product can be a pill,including capsule, a time-release oral dosage, a tablet, a gel capsule,a sub-lingual tablet or any oral dosage product. A pill may contain orbe made of any of the following, alone or in combination: an activeagent, a drug, a placebo, vitamins, or any food material. In accordancewith one aspect of the present invention, the product has the devicepositioned inside or secured to the interior of the product. In analternative arrangement, the device is secured to the exterior of theproduct.

Referring now to FIG. 1, an example of a pill 20 having a convex surfaceis shown with a marker assembly 22 secured on the outside. Additionally,the marker assembly 22 conforms to the shape of the pill 20. In thecurrent example, as shown in FIG. 2, the marker assembly 22 includes aningestible event marker or an ionic emission module (IEM) unit 24, alower protective layer 26, an upper protective layer 28, an adhesive orsecuring layer 30, and a decorative or printing layer 32. In accordancewith one aspect of the present invention, a non-conduction outer portionor skirt of the IEM unit 24 includes holes 24 a, as shown in FIG. 2Adistributed around the IEM unit 24 so that layers 26 and 28 maybelaminated together at connection 25, as shown in FIG. 1A, through theholes 24 a as the layers 26 and 28 are secured to or laminated onto theIEM unit 24.

Referring now to FIG. 1B and 26, in accordance with another aspect ofthe present invention, the protective player 26 and the securing layer30 of FIG. 1 are preplaced by a plurality of securing dots or portions27. As shown in FIG. 1C and 2C, in accordance with another aspect of thepresent invention, the protective player 26 is included and the securinglayer 30 of FIG. 1 is preplaced by a plurality of securing dots orportions 27. The marker assembly 22 is separated from the pill 20 by anair gap and, hence, able to be secured to the pill 20 regardless of theshape of the pill 20 since the dots 27 deform and adjust to contour tothe shape of the pill 20. Thus, when the shape of the pill 20 is suchthat the marker assembly 22 cannot be easily conformed to the shape ofthe pill 20, the dots 27 will deform and adapt. This ensures a secureconnection between the shape of the pill 20 and the shape of the markerassembly 22. The dots 27 are distributed about the marker assembly 22and used to connect the marker assembly 22 to the pill 20. Furthermore,the thickness or amount of securing materials needed to secure eachmarker assembly 22 to the pill 20 would be reduced.

The IEM unit 24 includes a control unit surrounded by the skirt and twodissimilar materials (not shown), each of which dissimilar material iselectrically connected to the control unit and isolated from each other.The dissimilar materials represent a portion of a power source or may bereferred to as a partial power source and when in contact with aconducting fluid, produce a voltage potential across the materials asthe materials dissolve. Once the IEM unit 24 comes into contact with aconducting fluid, such as body fluids found in the stomach, then the IEMunit 24 is activated and a current flow is produced by the dissimilarmaterials dissolving into solution and the voltage potential is producedbetween the dissimilar materials as they go from solid state tosolution.

According to another aspect of the present invention, the securing layer30 may also be replaced by a layer that includes the properties ofadhesion and releasing. For example, the release functionality isachieved by incorporating a disintegrant (e.g. Sodium starch glycolate)or water soluble excipient (e.g. Hydroxypropyl cellulose). Thus, thenwhen the assembly 22 gets wet, the layer 30 would eject the markerassembly 22 from the pill 20. Accordingly, to the extent that referenceis made in the present invention to an adhesive or securing layer, thescope of the present invention contemplates the use of either a layerthat has adhesive properties or a layer that has both adhesive andreleasing properties. The scope of the present invention is not limitedby the shape of the marker assembly 22. The IEM concept can be expandedto a “galvanic tablet” or dosage form where the drug release rate isgalvanically controlled by an integrated circuit (IC). The dosage formwould consist of a chip, connected to a partial power source (e.g. aCuCl-Mg materials similar to the material used with IEM), and alsoconnected to a matrix containing a drug compound. Once activated, the ICcontrols the rate of drug discharge by controlling the current orpotential applied to the matrix. An example of this is a matrixconsisting of a drug compound, a binder, and an electrochemicallysoluble material, e.g., a salt. Electrochemical conversion of the saltto a soluble species erodes or creates pores in the matrix that releasesthe drug at a precise rate corresponding to the charge passed.

The IC can control the charge applied to the matrix at any desirablerate, e.g., to achieve constant drug discharge, pulsatile discharge,gradually ramped drug delivery. Discharge can be in response to aphysiological signal sensed by the IC, e.g., local pH, impedance,motility, location in the GI tract, bleeding. Discharge can also beexternally triggered, e.g. the IC may contain an RF antenna that allowsthe patient or a medical monitor, e.g. personal health companion, bloodmonitor, to set off drug release in response to a physical conditionlike pain. IEM configurations of interest include, but are not limitedto: those described in: PCT application serial no. PCT/US20061016370published as WO/2006/116718; PCT application serial no.PCT/US2007/082563 published as WO/2008/052136; PCT application serialno. PCT/US2007/024225 published as WO/2008/063626; PCT applicationserial no. PCT/US2007/022257 published as WO/2006/066617; PCTapplication serial no. PCT/US2008/052845 published as WO/2008/095183;PCT application serial no. PCT/US2008/053999 published asWO/2008/101107; PCT application serial no. PCT/US2008/056296 publishedas WO/2008/112577; PCT application serial no. PCT/US2008/056299published as WO/2008/112578; PCT application serial no.PCT/US2008/077753 published as WO 2009/042812; U.S. patent applicationSer. No. 12/546,017; and U.S. Provisional Application Ser. Nos.61/142,849; 61/142,861; 61/173,511, 61/173,564; and 61/177,611; thedisclosures of which applications are herein incorporated by reference.

The dosage form is capable of providing very precise drug concentrationsin the blood, rapid dose delivery for pain management, or localizeddelivery in the GI tract. Medical applications may include GI disease,e.g., motility, colitis, pain management, localized delivery to tumors,customized dosing of therapeutics, e.g., immunosuppressants, and others.

Other release mechanisms are also possible: the drug matrix may containan electroactive drug-binding polymer, e.g. Nafion, proteins, whosestate of charge or degree of swelling can be altered by application of acurrent or potential. Application of a potential by the IC alters thebinding properties of the polymer to the drug to effectuate release ofthe drug. Another possible mechanism is that the IC controls theconcentration of a solution species around the dosage form. e.g. H+,which in turn can increase/decrease the solubility of the drug matrixand modulate drug release. The current may also be applied to an outerlayer of the dosage form rather than the entire matrix to control thedissolution rate of a coating.

The power source and the drug matrix can be distinct or the same. Forexample, a matrix may contain CuCl as the electrochemically activespecies. CuCl can act both as a cathode to power the IC and as a specieswhose conversion (to copper and chloride ions) releases the drug. The IClocation may be in the bulk of the dosage form or on the surface. Thesensors can be incorporated into the IC and used to trigger drug releaseor report physiological conditions to a receiver unit, e.g., pH,impedance, chemical sensor, temperature (detect bleeding). The sheath,coating, or manifold may be used to confine the matrix so thatdissolution occurs only at one surface while the other surfaces arecoated by a sheath that prevents dissolution. A coating may also beapplied to prevent drug release until the drug reaches a desiredlocation in the GI tract, e.g. intestine or colon.

One example of a pain management scenario is that there is usually abasal rate of pain relief from a long-acting opioid (e.g., Oxycontin)coupled with self-titrated short-acting opioid for breakthrough pain.This paradigm is used for both injectable and oral regimens. Thisinvention could handle both basal and breakthrough pain in the same pillor cluster of pills, or one could use the invention solely for thebreakthrough component, if the patient were also taking a standardlong-acting oral agent. This relates to conceiving of this as anIngestible Patient-Controlled Analgesia system (analogous to thein-hospital, IV-based PCA). One aspect of the present invention includesstably associating the IEM with a pharmaceutically inactive excipientmaterial designed to: 1) protect the IEM from moisture, handling and thenearby environment and 2) protect the active pharmaceutical elsewhere inthe formulation from damage or degradation by the IEM itself. One ormore protective IEM “sandwiches” could be developed such that the final.IEM plus excipient module could be reliably integrated into the finaltablet or capsule oral dosage form with minimal risk of deleteriouseffects on product dissolution or stability. Over time, oncecharacterization of IEM sandwich performance has been completed inassociation with active pharmaceuticals bracketing the range ofessential drug characteristics, e.g., pH, dissolution, bioavailability,solubility, regulatory clearance-related testing of an IEM-enabledmedication might be streamlined, leading to a quicker time-to-market forwhat would in essence become a new form of proprietary medication, onewhere the market exclusivity would not necessarily depend upon themolecular composition-of-matter patent, but on the incorporation of theIEM and the attendant capabilities enabled by such incorporation.

Referring now to FIG. 3A, a pill 40 having a near planar or flat surfaceis shown with a marker assembly 42 secured on the outside. The markerassembly 42 conforms to the shape of the pill 40. In the currentexample, the marker assembly 42 includes an IEM unit 44, a lowerprotective layer 46, an upper protective layer 48, an adhesive orsecuring layer 50 and a decorative or printing layer 52.

Referring now the FIG. 3B, in accordance with another aspect of thepresent invention, the pill 40 is shown with a first tablet portion 41.A marker assembly 42 a is shown secured to the surface of the firsttablet portion 41. The marker assembly 42 a is covered by a secondtablet portion 43. The portion 41 and the portion 43 may be similar ordifferent materials. For example, in accordance with one aspect of thepresent invention, the portion 41 may be the drug product and theportion 43 may be fast dissolving material. The marker assembly 42 a maybe similar to the marker assembly 42 of FIG. 3A or it may simply be justthe IEM unit 44 with the lower layer 46 and the upper layer 48.

Referring now to FIG. 3B and FIG. 3C, in accordance with another aspectof the present invention, the marker assembly 42 a may be replaced bythe marker assembly 42 b of FIG. 3C. The marker assembly 42B includesthe IEM unit 44 and a lamination or film coating 45. The laminated layeris made of a dissolvable material that delays the activation of the IEMunit 44 once the portion 41 and portion 43 of the pill 40 have dissolvedor disintegrated to release the marker assembly 42 b. The film coating45 may be made of a variety of materials or films, such as polymerfilms, including polyethylene oxide, hydroxypropyl cellulose, andtriethyl citrate. Other films that can be used include any dissolvablepolymer or plasticizer. The film coating 45 provides a moisture barrierand dissolves under the proper conditions to delay activation of the IEMunit 44. The film coating 45 is designed to provide sufficient delay inexposure of the IEM unit to the surrounding fluids relative to thedisintegration and dispersion of the pill 40. The film coating 45 mayinclude any of the following: soluble materials, barrier materials (suchas lipids, polyvinyl alcohol), processing aids (such as plasticizers,adhesion promoters), and stabilizers. Furthermore, the film coating 45may be manufactured via lamination, application of a coating solution orslurry followed by a cure. For example, in accordance with one aspect ofthe present invention, the film coating 44 may be laminated to the IEMunit 44, wherein the edge or extremities of the IEM unit 44 are exposedas shown in FIG. 3A. For example, in accordance with another aspect ofthe present invention, the film coating 44 may be laminated around theIEM unit 44 to form a pocket, wherein the edge or extremities of the IEMunit 44 are covered as shown in FIG. 3B. In accordance with otheraspects of the present invention, the film coating 45 may be formedaround the IEM unit 44 using dry compression, such as a tablet press.

It will also be apparent that the various layers disclosed can beeliminated or combined depending on the material employed and theproperties thereof. For example, referring to FIG. 2, the lowerprotective layer 26 and securing layer 30 may be combined into a singlelayer, which is shown in FIG. 4. More specifically and referring to FIG.4, a pill 52 is shown having a convex surface, although a planar orconcave surface may be employed without limiting the scope of thepresent invention. A marker assembly 54 is secured to the pill 52. Inthe current example, the marker assembly 54 includes a lower layer 56,an upper layer 58, and a device 60, such as an IEM. According to oneaspect of the present invention, the lower layer 56 is a material thatcombines both the adhesive and protective properties of layer 30 andlayer 26 of FIG. 2, respectively. In a similar manner, upper layer 58 isa material that combines the protective and decorative properties oflayer 28 and layer 32 of FIG. 2, respectively. Also, in the currentexample, the marker assembly 54 is a different size relative to the pill52. The scope of the present invention is not limited by the shape orsize of the marker assembly 54 in this example or any other exampledisclosed herein.

Referring now to FIG. 5, a pill 62 is shown having a convex surface,although a planar or concave surface may be employed without limitingthe scope of the present invention. A marker assembly 64 is secured tothe pill 62. In the current example, the marker assembly 64 includes anupper layer 66 and a device 68, such as an IEM. In the current example,the adhesive layer and its properties, such as the adhesive layer 30 ofFIG. 2, may be part of the coating on the pill 62. Alternatively,according to another aspect of the present invention, the adhesive layermay be part of the device 68. In yet another aspect of the presentinvention the adhesive properties may be provided by the upper layer 66at the contact points with the pill 62. Thus, depending on theproperties of the materials selected, the properties of each layer canbe altered to the specific needs of that aspect as shown in the variousexamples.

Referring now to FIG. 5A, the process of assembling the marker assembly64 onto the pill 62 is shown in accordance with one aspect of thepresent invention. The marker assembly 64 is built one layer at a timeonto the pill 62. The device 68 is positioned on the pill 62. The device68 is then formed to the shape of the pill 62. The device 68 can beshaped to the shape of the pill 62 using any standard method, e.g., heatand/or pressure. Then the upper layer 66 is added and shaped to theshape of the pill 62 as well as secured thereto using pressure and/orheat.

Referring now to FIG. 5B, the process of assembling the marker assembly64 onto the pill 62 is shown in accordance with another aspect of thepresent invention. In this example, the marker assembly 64 is assembledprior to being presented to the pill 62. The marker assembly 64 ispositioned on the pill 62. Then the marker assembly 64 is secured to andformed to the shape of the pill 62 using heat and/or pressure.

Referring now to FIG. 6 and FIG. 6A, in yet another example according toanother aspect of the present invention, a pill 70 includes a convexsurface, although a planar or concave surface may be employed withoutlimiting the scope of the present invention. A marker assembly 72 isformed to the shape of and secured to the pill 70 using heat and/orpressure. In the current example, the marker assembly 72 includes adevice coating layer 74 and a device 74 a, such as an IEM. In thecurrent example, the adhesive layer and its properties and theprotective layer and its properties, such as the adhesive layer 30 andprotective layers 26 and 28 of FIG. 2, are part of the device coatinglayer 74. Additionally, the properties of the decorative layer 32 ofFIG. 2 may also be part of the device coating layer 74.

Referring now to FIG. 7, in yet another example according to anotheraspect of the present invention, a pill 76 includes a convex surface,although a planar or concave surface may be employed without limitingthe scope of the present invention. A marker 78 is secured to the pill76. An enclosing layer 80 surrounds the pill 76 and the marker 78. Inthe current example, the properties of the adhesive layer, theprotective layers, and the decorative layer (such as the layer 30 andlayers 26/28 and layer 32 of FIG. 2, respectively) may be part of theenclosing layer 80. In an alternative aspect of the present invention,the marker 78 may have the adhesive properties instead of or in additionto the enclosing layer 80.

Referring now to FIG. 8, in yet another example according to anotheraspect of the present invention, a capsule 84 is shown. A marker 86 issecured to one end of the capsule 84. A layer 88 surrounds the marker 86and is also secured to the capsule. In the current example, theproperties of the adhesive layer, the protective layers, and thedecorative layer (such as the layer 30 and layers 26/28 and layer 32 ofFIG. 2, respectively) may be incorporated into the layer 88. In analternative aspect of the present invention, the marker 86 may have theadhesive properties instead of or in addition to the layer 88.

Referring now to FIG. 9, in yet another example according to anotheraspect of the present invention, a capsule 90 is shown. A markerassembly 92 is secured to mid-portion the capsule 90. The markerassembly 92 surrounds the circumference of the capsule 90. However, themarker assembly 92 may be designed to only partially surround thecapsule 90 (not shown). In accordance with another aspect of the presentinvention. In the current example, the properties of the adhesive layer,the protective layers, and the decorative layer (such as the layer 30and layers 26/28 and layer 32 of FIG. 2, respectively) may beincorporated into the marker assembly 92.

Referring now to FIG. 10, the process steps of securing a device or adevice assembly onto a tablet or pill is shown beginning with the step100 wherein a raw core tablet or pill is created. At step 102, thedevice or the device assembly is attached to the raw core tablet tocreate an assembled tablet. At step 104, a sub coating is added to theassembled tablet to create a coated tablet. At step 106, which is anoptional step, color coating is added to the coated tablet to create acolor coated tablet. At step 108, which is an optional step, the colorcoated tablet is imprinted to produce an imprinted tablet that is readyfor distribution.

Referring now to FIG. 11, the process steps of securing a device or adevice assembly onto a tablet or pill in accordance with another aspectof the present invention is shown beginning with the step 110 wherein araw core tablet or pill is created. At step 112, a sub coating is addedto the raw core tablet to create a coated tablet. At step 114, thedevice or the device assembly is attached to the coated tablet to createan assembled coated tablet. At step 116, which is an optional step,color coating is added to the assembled coated tablet to create a colorcoated tablet. At step 118, which is an optional step, the color coatedtablet is imprinted to produce an imprinted tablet that is ready fordistribution.

Referring now to FIG. 12, the process steps of securing a device or adevice assembly onto a tablet or pill in accordance with yet anotheraspect of the present invention is shown beginning with the step 120wherein a raw core tablet or pill is created. At step 122, a sub coatingis added to the raw core tablet to create a coated tablet. At step 124,color coating is added to the coated tablet to create a color coatedtablet. At step 126, a device or the device assembly is attached to thecolor coated tablet to create an assembled color coated tablet. At step128, a second coating is added to the assembled color coated tablet tocreate an enclosed assembled tablet. At step 129, which is an optionalstep, the enclosed assembled tablet is imprinted to produce an imprintedtablet that is ready for distribution.

Referring now to FIG. 14. FIG. 15, and FIG. 16, a tablet press 150 isshown. The press 150 rotates in a counter-clockwise direction as shown.The press 150 includes die cavity or punch cavity 152 and an ejectiontray 154. Starting at position A, as shown, the pharmaceutical productis deposited in the cavity 152, The press 150 rotates to position B,which is positioned below a transfer wheel 160. The wheel 160 includesseveral openings 162. As the wheel 160 passes position C, each opening162 passes under a feeder 170, as shown in FIG. 16.

The feeder 170 contains marker devices 200. The device 200 is an IEMthat is activated upon contact with a conducting fluid. The scope of thepresent invention is not limited by the environment or type of theconducting fluid. Once ingested, the device 200 comes into contact witha conducting fluid, such as stomach fluids, and the device 200 isactivated. Referring again to the instance where the device 200 is usedwith the product that is ingested by the living organism, when theproduct that includes the device 200 is taken or ingested, the device200 comes into contact with the conducting liquid of the body and avoltage potential is created and the system is activated. A portion ofthe power source is provided by the device 200, while another portion ofthe power source is provided by the conducting fluid.

Referring again to FIG. 14 and FIG. 15, each time an opening 162 passesunder the feeder 170, one of the devices 200 is dropped into the opening162 directly under the feeder 170. As shown in FIG. 15, a force “F” isshown to assist the movement of the device 200 from the feeder 170 intothe opening 162. The force may be provided by the use of a vacuumthrough a suction tube 168. In accordance with other aspects of thepresent invention, the force may be provided by a spring, an air burst,or an ejection pin in addition to gravity. The wheel 160 rotates toposition B. At position B, the device 200 located in the opening 162 isdropped into the cavity 152 of the press 150. The press 150 rotates tothe position D where additional pharmaceutical product is deposited intothe cavity 152 on top of the device 200. The press 150 continues to movein the counter-clockwise direction and at position E, the content of thecavity 152 is pressed under high pressure to form a tablet with thedevice 200 inside. The completed tablet is ejected and moved to acollection point through the ejection tray 154 for further processing,such as coating layers as needed.

Referring now to FIG. 17, a feeder assembly 172 is shown as alternativeembodiment and in accordance with another aspect of the presentinvention. The feeder assembly 172 can be used in place of the feeder170 of the FIG. 14. The feeder assembly 172 includes a plurality ofsupporting fingers 174 that hold each device 200 in position. Thefingers 174 are connected to a belt 176. The fingers 174 lower thedevice 200 toward the wheel 160 of FIG. 14. When the fingers 174 reachthe lower portion near the wheel 160, the fingers 174 move apart anddrop the device 200 into the opening 162 of the wheel 160.

Referring now to FIG. 18A and FIG. 188, in accordance with anotheraspect of the present invention, the feeder assembly 172 includes anejector 173 with a spring 175. As the opening 162 moves under the feederassembly 172, the ejector 173 pushes the device 200 into the opening 162of the wheel 160.

Referring now to FIG. 24A, FIG. 24B, and FIG. 24C, an alternativeexample of a feeder assembly 170 a is shown positioned below a cuttingtool 170 b. A web sheet 177 is positioned between the feeder assembly170 a and the tool 170 b. The web sheet 177 delivers devices 179 to aposition above the feeder assembly 170 a. As shown in FIG. 24B, the tool170 b moves toward the feeder assembly 170 a and cuts out the device179. An ejector 170 c moves downward to push the device 179 out of thetool 170 b and into the feeder assembly 170 a. As shown in FIG. 24C, theprocess continues and the devices 179 are fed into the feeder assembly170 a. This process can be used to load the feeder 170 of FIG. 16. Inaccordance with another aspect of the present invention, the feederassembly 170 a can be used to replace the feeder 170 of FIG. 14 and FIG.16.

Referring now to FIG. 13, the process steps of assembling a device 200within the tablet or pill is shown beginning with the step 130 whereinthe powder/raw material is loaded into the mold, At step 132 the device200 is inserted into the mold. At step 134 more powder/raw material isadded and a raw core tablet or pill is created. At step 134 a coatinglayer is added to the raw core tablet to create a coated tablet. At step138, color coating is added to the coated tablet to create a colorcoated tablet. At step 139, which is an optional step, the color coatedtablet is imprinted to produce an imprinted tablet that is ready fordistribution.

In accordance with another aspect of the present invention, the device200 may be secured to the exterior of the product. The process ofassembling or securing the device 200 to the exterior of the product canbe done using an assembly array. Referring now to FIG. 19 and FIG. 20, awheel 180 is shown that includes positional grooves 182. The grooves 182are shown in greater detail in FIG. 20. Each groove 182 has an opening184 therein. A vacuum is created through the opening 184 that drawspills 186 into position as the pills 186 are delivered to the wheel 180from a hopper tray 188. In accordance with other aspects of the presentinvention, the pills 186 can be positioned by other methods than vacuumdraw. The pills 186 can be vibrated into position or brushed over withsome form of sweeper so they fall into the hole and excess are brushedoff. As the wheel 180 rotates the pill 186 moves to station 1 where anadhesive layer is applied. As the wheel 180 moves to station 2, thedevice 200 is secured to each pill 186. As the wheel 180 moves tostation 3 a protective layer is applied. As the wheel 180 moves tostation 4, a decorative or printed layer is applied. Thereafter, thecomplete and printed tablets or pills 186 are removed from the wheel 180to a central collection point for further processing or distribution.The scope of the present invention is not limited by the number ofstations on the wheel 180. For example, there wheel 180 can be designedto have one station, at which station a pre-assembled device is appliedto the pill 186. The pre-assembled device can be as simple as the IEMwith an adhesive layer or as discussed above with respect to FIG. 1.

Referring now to FIG. 21, at each station shown in FIG. 19 variousassembly steps are carried out including installation of the device onthe tablet as well as other components or parts. A portion of a deliveryarm 230 is shown positioned over a portion of the pills 186. Thedelivery arm 230 moves between the wheel 180 and a web 232. The web 232contains devices 234 arranged in order to allow for the delivery arm 230to pick up the devices 234. The delivery arm 230 removes the devices 234from the web 232 and secures the devices 234 to the pills 186. Inaccordance with another aspect of the present invention the devices 234are cut or punched out of the web 232. At other stations, other deliveryarms remove or punch out or cut out other materials from different webrolls and secure those materials to the pills 186. For example, thedelivery arm can remove a protection layer from the web sheet and secureit to a tablet with a device already secured thereto. According toanother aspect of the present invention, the devices positioned on theweb may be a marker assembly unit such that a single installationprocess is all that is needed and each station can be used to performthe single task of moving the marker assembly from the web to the pill186 using the delivery arm 230.

Referring now to FIG. 22, an assembly process is shown wherein a tool210 includes a cavity 212. The tool 210 is positioned above an assemblydevice 214, which includes circuitry 214 a, prior to formation of thedevice onto a pill or tablet 216. The tool 210 is formed to the shape ofthe tablet 216 and is lowered onto the device 214. Through theapplication of temperature and pressure the device 214 is reformed asdevice 218 and secured to the tablet 216 as device 220. The cavity 212prevents pressure from being applied to the circuitry 214 a of thedevice 214.

Referring now to FIG. 23A, FIG. 23B, and FIG. 23C, according to anotheraspect of the present invention, an alternative assembly process isshown wherein a pressing tool or cutting tool 240 is positioned above apress table 242. The table 242 includes grooves 246 that have a centralhole 248. The tablet 250 is held in the groove 246 using a vacuumsuction applied through the hole 248. A web sheet 252 is positionedbetween the table 242 and the tool 240. The sheet 252 includes devices254. To begin the assembly process, the tool 240 moves toward the table242. The sheet 252 is punched and the device 254 is secured to thetablet 250 as shown in FIG. 238. At a different station or position inthe assembly process, a sheet 256 that includes a different layer in theassembly process is positioned between the table 242 that now holds thetablet 250 with the device 254 secured thereto and a cutting tool 260.The cutting tool 260 moves toward the table 242 and secures the layer256 onto the tablet 250 (not shown) to form a coated tablet 250 with adevice 254 assembled thereto.

Referring now to FIG. 25, an assembly process is shown in accordancewith another aspect of the present invention. An assembly unit 300includes a press 302 and a press 304. The press 302 is positioned abovea web 308. The web 308 has devices 306 positioned and held in place onthe web 308. Devices 306 have an adhesive layer holding them to the web308 and a second adhesive layer positioned on the opposite side adjacentto the tablets 312. As the web 308 moves from a roller 310 a to a roller310 b, the devices are presented and positioned above tablets 312, whichare positioned on a tablet feeder belt 314. The feeder belt 314 movesthe tablets 312 towards the press 304 as the devices 306 move toward thepress 302. As the tablets 312 approach the press 304, each tablet 312falls into a groove 304 a of the press 304. The tablet 312 is thenlifted by the press 304 toward the press 302 as the press 302 pushes thedevice 306 toward the press 304. At position 318 the device 306 ispressed onto the tablet 312 and secured thereto. As the press 302 andpress 304 rotate the web 308 moves toward the roller 310 b. At the sametime, an assembled tablet 320 is lowered onto a take away roller belt322 that moves the assembled tablet 320 away from the press 302 and thepress 304. The assembled tablets 320 may be moved to the next phase ofthe process including packaging for distribution or additionalpreparation steps such as adding additional layers or coatings.

Embodiments of interest include high-throughput fabrication processes,e.g., where details regarding such embodiments are provided above and/orin U.S. Provisional Application Ser. No. 61/142,849; the disclosure ofwhich is herein incorporated by reference.

As described herein, a system of the present invention is used with aconducting fluid to indicate the event marked by contact between theconducting fluid and the system. For example, the system of the presentdisclosure may be used with a pharmaceutical product and the event thatis indicated is when the product is taken or ingested. The term“ingested” or “ingest” or “ingesting” is understood to mean anyintroduction of the system internal to the in-vivo. For example,ingesting includes simply placing the system in the mouth all the way tothe descending colon. Thus, the term ingesting refers to any instant intime when the system is introduced to an environment that contains aconducting fluid. Another example would be a situation when anon-conducting fluid is mixed with a conducting fluid, in such asituation the system would be present in the non-conduction fluid andwhen the two fluids are mixed, the system comes into contact with theconducting fluid and the system is activated. Yet another example wouldbe the situation when the presence of certain conducting fluids neededto be detected In such instances, the presence of the system, whichwould be activated, within the conducting fluid could be detected and,hence, the presence of the respective fluid would be detected.

It is noted that, as used herein and in the appended claims, thesingular forms “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely,” “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation,

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentinvention. Any recited method can be carried out in the order of eventsrecited or in any other order which is logically possible.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

Accordingly, the preceding merely illustrates the principles of theinvention. It will be appreciated that those skilled in the art will beable to devise various arrangements which, although not explicitlydescribed or shown herein, embody the principles of the invention andare included within its spirit and scope. Furthermore, all examples andconditional language recited herein are principally intended to aid thereader in understanding the principles of the invention and the conceptscontributed by the inventors to furthering the art, and are to beconstrued as being without limitation to such specifically recitedexamples and conditions. Moreover, all statements herein recitingprinciples, aspects, and embodiments of the invention as well asspecific examples thereof, are intended to encompass both structural andfunctional equivalents thereof. Additionally, it is intended that suchequivalents include both currently known equivalents and equivalentsdeveloped in the future, i.e., any elements developed that perform thesame function, regardless of structure. The scope of the presentinvention, therefore, is not intended to be limited to the exemplaryembodiments shown and described herein. Rather, the scope and spirit ofpresent invention is embodied by the appended claims

1-21. (canceled)
 22. A device for placement within a capsule, the devicecomprising: an assembly, including: a unit comprising a partial powersource; and a non-conductive membrane secured to the unit, wherein thenon-conductive membrane is configured to engage an inner wall of thecapsule to hold the device in place within the capsule.
 23. The deviceof claim 22, further comprising a protective coating surrounding theassembly.
 24. The device of claim 22, further comprising a firstprotective layer secured to an upper surface of the assembly and asecond protective layer secured to a lower surface of the assembly. 25.The device of claim 24, wherein the first protective layer and thesecond protective layer are secured to each other through a plurality ofholes defined in the non-conductive membrane.
 26. The device of claim24, wherein the first protective layer and the second protective layerare secured to each other at the edge of the assembly and extend beyondthe perimeter of the assembly such that the assembly is enclosed withinthe protective layers.
 27. The device of claim 22, wherein the unitincludes: a first material secured to a support structure; and a secondmaterial secured to the support structure and electrically isolated fromthe first material, such that the first material and the second materialrepresent a chemical voltage potential when in contact with a conductingfluid.
 28. The device of claim 27, wherein the support structurecomprises a control unit electrically connected to the first materialand the second material to control conductance between the firstmaterial and the second material, and wherein the control unit encodesinformation in a current signature by altering the conductance.
 29. Thedevice of claim 22, wherein the assembly further comprises an adhesivelayer to secure the device within the capsule.
 30. The device of claim29, wherein the adhesive layer is configured to release the device fromthe capsule after exposure to a fluid.
 31. The device of claim 22,wherein the assembly is configured to conform to a shape of the capsule.32. The device of claim 22, wherein the assembly is configured to engagethe inner wall to surround at least a portion of the circumference ofthe capsule.
 33. The device of claim 22, wherein the capsule comprises afirst end and a second end, and wherein the assembly is configured toengage the inner wall between the first end and the second end.
 34. Adevice for positioning inside a pharmaceutical product, the devicecomprising: an assembly, including: a control unit; a partial powersource comprising a first material and a second material, wherein thefirst material and the second material are electrically coupled to thecontrol unit; and a skirt attached to the control unit, wherein theskirt isolates the first material from the second material, and whereinthe skirt is configured to engage an internal surface of thepharmaceutical product.
 35. The device of claim 34, further comprisingat least one protective layer secured to the assembly.
 36. The device ofclaim 34, wherein the assembly further comprises an adhesive layer tosecure the device within the pharmaceutical product, and wherein theadhesive layer is configured to release the device from thepharmaceutical product after exposure to a fluid.
 37. The device ofclaim 34, wherein the assembly is configured to conform to a shape ofthe pharmaceutical product.
 38. The device of claim 34, wherein thepharmaceutical product comprises a capsule, and wherein the assembly isconfigured to engage the internal surface to surround at least a portionof the circumference of the capsule between a first end and a second endof the capsule.
 39. The device of claim 34, further comprising aprotective coating configured to dissolve after exposure to a fluid todelay activation of the device.
 40. A device for inclusion with acapsule, the device comprising: an assembly, including: a control unitelectrically coupled to a partial power source; and a non-conductivemembrane surrounding the control unit, wherein the non-conductivemembrane is configured to engage a surface of the capsule; wherein theassembly engages the surface to surround at least a portion of thecircumference of the capsule between a first end and a second end of thecapsule.
 41. The device of claim 40, wherein the assembly furthercomprises an adhesive layer to secure the device to the capsule, andwherein the adhesive layer is configured to release the device from thecapsule after exposure to a fluid.